title: Extracellular heat shock proteins: a new location, a new function.
abstract: The expression of heat shock proteins (HSPs) is a basic and well-conserved cellular response to an array of stresses. These proteins are involved in the repair of cellular damage induced by the stress, which is necessary for the salutary resolution from the insult. Moreover, they confer protection from subsequent insults, which has been coined stress tolerance. Because these proteins are expressed in subcellular compartments, it was thought that their function during stress conditions was circumscribed to the intracellular environment. However, it is now well established that HSPs can also be present outside cells where they appear to display a function different than the well-understood chaperone role. Extracellular HSPs act as alert stress signals priming other cells, particularly of the immune system, to avoid the propagation of the insult and favor resolution. Because the majority of HSPs do not possess a secretory peptide signal, they are likely to be exported by a nonclassic secretory pathway. Different mechanisms have been proposed to explain the export of HSPs, including translocation across the plasma membrane and release associated with lipid vesicles, as well as the passive release after cell death by necrosis. Extracellular HSPs appear in various flavors, including membrane-bound and membrane-free forms. All of these variants of extracellular HSPs suggest that their interactions with cells may be quite diverse, both in target cell types and the activation signaling pathways. This review addresses some of our current knowledge about the release and relevance of extracellular HSPs.
authors.affiliation: *Center for Investigations of Health and Education Disparities; †Division of Trauma, Surgical Critical Care and Burns, Department of Surgery; and ‡Department of Neurosciences, School of Medicine University of California San Diego, La Jolla, California; and §Department of Surgery, South Florida University, Tampa, Florida.
authors.forename: Antonio
authors.initials: A
authors.lastname: De Maio
authors.forename: Daniel
authors.initials: D
authors.lastname: Vazquez
mesh_terms: D055252:Cell-Derived Microparticles / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009336:Necrosis / Q000503:physiopathology
chemical_list: D006360:Heat-Shock Proteins